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The orexin receptor (OX) is critically involved in motivation and sleep-wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([ 11 C]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC 50 = 0.253 μM and 1.406 μM for OX 1 R and OX 2 R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [ 11 C]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [ 11 C]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.

A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging